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Recently, Ades and colleagues discussed the controversies and advancements in network meta-analysis (NMA) over the past two decades, discussing its reliability, assumptions, novel approaches, and provided some useful recommendations for the conduction of NMAs. The present discussion paper builds on the insights by Ades and colleagues, providing a roadmap for NMA applications, advancements in software and tools, and approaches designed to facilitate the assessment and interpretation of NMA findings. It also discusses the impact of NMA across disciplines, particularly for policymakers and guideline developers. Despite 20 years of NMA history, challenges remain in understanding and assessing assumptions, communicating and interpreting findings, and applying common approaches like network meta-regression and NMA involving non-randomized studies in readily available software. NMA has proven particularly valuable in clinical decision-making, which highlights the need for additional training and interdisciplinary collaboration of knowledge users, including patient engagement, to enhance its adoption and address real-world problems.
Subject(s)
Nitric Oxide , Piperazines , Purines , Sildenafil Citrate , Sulfones , Vasodilator Agents , Humans , Sildenafil Citrate/administration & dosage , Sildenafil Citrate/therapeutic use , Infant, Newborn , Nitric Oxide/administration & dosage , Administration, Inhalation , Purines/administration & dosage , Purines/therapeutic use , Piperazines/administration & dosage , Piperazines/therapeutic use , Vasodilator Agents/administration & dosage , Vasodilator Agents/therapeutic use , Sulfones/administration & dosage , Sulfones/therapeutic use , Persistent Fetal Circulation Syndrome/drug therapy , Hypertension, Pulmonary/drug therapyABSTRACT
BACKGROUND: Conflicts of interest (COIs) of contributors to a guideline project and the funding of that project can influence the development of the guideline. Comprehensive reporting of information on COIs and funding is essential for the transparency and credibility of guidelines. OBJECTIVE: To develop an extension of the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement for the reporting of COIs and funding in policy documents of guideline organizations and in guidelines: the RIGHT-COI&F checklist. DESIGN: The recommendations of the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network were followed. The process consisted of registration of the project and setting up working groups, generation of the initial list of items, achieving consensus on the items, and formulating and testing the final checklist. SETTING: International collaboration. PARTICIPANTS: 44 experts. MEASUREMENTS: Consensus on checklist items. RESULTS: The checklist contains 27 items: 18 about the COIs of contributors and 9 about the funding of the guideline project. Of the 27 items, 16 are labeled as policy related because they address the reporting of COI and funding policies that apply across an organization's guideline projects. These items should be described ideally in the organization's policy documents, otherwise in the specific guideline. The remaining 11 items are labeled as implementation related and they address the reporting of COIs and funding of the specific guideline. LIMITATION: The RIGHT-COI&F checklist requires testing in real-life use. CONCLUSION: The RIGHT-COI&F checklist can be used to guide the reporting of COIs and funding in guideline development and to assess the completeness of reporting in published guidelines and policy documents. PRIMARY FUNDING SOURCE: The Fundamental Research Funds for the Central Universities of China.
Subject(s)
Checklist , Conflict of Interest , Practice Guidelines as Topic , Humans , Research Support as Topic/ethics , DisclosureABSTRACT
BACKGROUND: Thrombocytopenia is a prevalent presentation in childhood with a broad spectrum of etiologies, associated findings, and clinical outcomes. Establishing the cause of thrombocytopenia and its proper management have obvious clinical repercussions but may be challenging. This article provides an adaptation of the high-quality Clinical Practice Guidelines (CPGs) of pediatric thrombocytopenia management to suit Egypt's health care context. METHODS: The Adapted ADAPTE methodology was used to identify the high-quality CPGs published between 2010 and 2020. An expert panel screened, assessed and reviewed the CPGs and formulated the adapted consensus recommendations based on the best available evidence. DISCUSSION: The final CPG document provides consensus recommendations and implementation tools on the management of isolated thrombocytopenia in children and adolescents in Egypt. There is a scarcity of evidence to support recommendations for various management protocols. In general, complete clinical assessment, full blood count, and expert analysis of the peripheral blood smear are indicated at initial diagnosis to confirm a bleeding disorder, exclude secondary causes of thrombocytopenia and choose the type of work up required. The International Society of Hemostasis and thrombosis-Bleeding assessment tool (ISTH-SCC BAT) could be used for initial screening of bleeding manifestations. The diagnosis of immune thrombocytopenic purpura (ITP) is based principally on the exclusion of other causes of isolated thrombocytopenia. Future research should report the outcome of this adapted guideline and include cost-analysis evaluations.
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AIM: To determine the comparative effectiveness of fluid schemes for children with diabetic ketoacidosis (DKA). METHODS: We conducted a systematic review with an attempt to conduct network meta-analysis (NMA). We searched MEDLINE, EMBASE, CENTRAL, Epistemonikos, Virtual Health Library, and gray literature from inception to July 31, 2022. We included randomized controlled trials (RCTs) in children with DKA evaluating any intravenous fluid schemes. We planned to conduct NMA to compare all fluid schemes if heterogeneity was deemed acceptable. RESULTS: Twelve RCTs were included. Studies were heterogeneous in the population (patients and DKA episodes), interventions with different fluids (saline, Ringer's lactate (RL), and polyelectrolyte solution-PlasmaLyte®), tonicity, volume, and administration systems. We identified 47 outcomes that measured clinical manifestations and metabolic control, including single and composite outcomes and substantial heterogeneity preventing statistical combination. No evidence was found of differences in neurological deterioration (main outcome), but differences were found among interventions in some comparisons to normalize acid-base status (â¼2 h less with low vs. high volume); time to receive subcutaneous insulin (â¼1 h less with low vs. high fluid rate); length of stay (â¼6 h less with RL vs. saline); and resolution of the DKA (â¼3 h less with two-bag vs. one-bag scheme). However, available evidence is scarce and poor. CONCLUSIONS: There is not enough evidence to determine the best fluid therapy in terms of fluid type, tonicity, volume, or administration time for DKA treatment. There is an urgent need for more RCTs, and the development of a core outcome set on DKA in children.
Subject(s)
Diabetic Ketoacidosis , Fluid Therapy , Humans , Diabetic Ketoacidosis/therapy , Fluid Therapy/methods , Child , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVES: To compare the efficacy of influenza vaccines of any valency for adults 60 years and older. DESIGN AND SETTING: Systematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE, JBI Evidence-Based Practice (EBP) Database, PsycINFO, and Cochrane Evidence -Based Medicine database were searched from inception to 20 June 20, 2022. Two reviewers screened, abstracted, and appraised articles (Cochrane Risk of Bias (ROB) 2.0 tool) independently. We assessed certainty of findings using Confidence in Network Meta-Analysis and Grading of Recommendations, Assessment, Development and Evaluations approaches. We performed random-effects meta-analysis and network meta-analysis (NMA), and estimated odds ratios (ORs) for dichotomous outcomes and incidence rate ratios (IRRs) for count outcomes along with their corresponding 95% confidence intervals (CIs) and prediction intervals. PARTICIPANTS: Older adults (≥60 years old) receiving an influenza vaccine licensed in Canada or the USA (vs placebo, no vaccine, or any other licensed vaccine), at any dose. MAIN OUTCOME MEASURES: Laboratory-confirmed influenza (LCI) and influenza-like illness (ILI). Secondary outcomes were the number of vascular adverse events, hospitalisation for acute respiratory infection (ARI) and ILI, inpatient hospitalisation, emergency room (ER) visit for ILI, outpatient visit, and mortality, among others. RESULTS: We included 41 RCTs and 15 companion reports comprising 8 vaccine types and 206 032 participants. Vaccines may prevent LCI compared with placebo, with high-dose trivalent inactivated influenza vaccine (IIV3-HD) (NMA: 9 RCTs, 52 202 participants, OR 0.23, 95% confidence interval (CI) (0.11 to 0.51), low certainty of evidence) and recombinant influenza vaccine (RIV) (OR 0.25, 95%CI (0.08 to 0.73), low certainty of evidence) among the most efficacious vaccines. Standard dose trivalent IIV3 (IIV3-SD) may prevent ILI compared with placebo, but the result was imprecise (meta-analysis: 2 RCTs, 854 participants, OR 0.39, 95%CI (0.15 to 1.02), low certainty of evidence). Any HD was associated with prevention of ILI compared with placebo (NMA: 9 RCTs, 65 658 participants, OR 0.38, 95%CI (0.15 to 0.93)). Adjuvanted quadrivalent IIV (IIV4-Adj) may be associated with the least vascular adverse events, but the results were very uncertain (NMA: eight 8 RCTs, 57 677 participants, IRR 0.18, 95%CI (0.07 to 0.43), very low certainty of evidence). RIV on all-cause mortality may be comparable to placebo (NMA: 20 RCTs, 140 577 participants, OR 1.01, 95%CI (0.23 to 4.49), low certainty of evidence). CONCLUSIONS: This systematic review demonstrated efficacy associated with IIV3-HD and RIV vaccines in protecting older persons against LCI. RIV vaccine may reduce all-cause mortality when compared with other vaccines, but the evidence is uncertain. Differences in efficacy between influenza vaccines remain uncertain with very low to moderate certainty of evidence. PROSPERO REGISTRATION NUMBER: CRD42020177357.
Subject(s)
Influenza Vaccines , Influenza, Human , Network Meta-Analysis , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Aged , Middle Aged , Randomized Controlled Trials as Topic , Hospitalization/statistics & numerical dataABSTRACT
Pediatric transfusion is a complex area of medicine covering a wide age range, from neonates to young adults. Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines. We aimed to adapt the pre-existing high-quality practice guidelines for the transfusion of blood components in different pediatric age groups to be available for national use by general practitioners, pediatricians, and other health care professionals. The guideline panel included 17 key leaders from different Egyptian institutions. The panel used the Adapted ADAPTE methodology. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of the indications, dosing, and administration of packed red cells, platelets, and fresh frozen plasma. It also included transfusion in special situations, e.g., chronic hemolytic anemia and aplastic anemia, management of massive blood loss, malignancies, surgery, recommendations for safe transfusion practices, and recommendations for modifications of cellular blood components. The final version of the adapted clinical practice guideline (CPG) has been made after a thorough review by an external review panel and was guided by their official recommendations and modifications. A set of implementation tools included algorithms, tables, and flow charts to aid decision-making in practice. This adapted guideline serves as a tool for safe transfusion practices in different pediatric age groups.
Subject(s)
Blood Component Transfusion , Evidence-Based Medicine , Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Young Adult , Blood Transfusion , Egypt , Evidence-Based Medicine/methods , HemorrhageABSTRACT
OBJECTIVES: A core outcome set (COS) is an agreed standardized set of outcomes that should be measured and reported, as a minimum, in specific areas of health or health care. A COS is developed through a consensus process to ensure health care outcomes to be measured are relevant to decision-makers, including patients and health-care professionals. Use of COS in guideline development is likely to increase the relevance of the guideline to those decision-makers. Previous work has looked at the uptake of COS in trials, systematic reviews, health technology assessments and regulatory guidance but to date there has been no evaluation of the use of COS in practice guideline development. The objective of this study was to investigate the representation of core outcomes in a set of international practice guidelines. STUDY DESIGN AND SETTING: We searched for clinical guidelines relevant to ten high-quality COS (with focus on the United Kingdom, Germany, China, India, Canada, Denmark, United States and World Health Organisation). We matched scope between COS and guideline in terms of condition, population and outcome. We calculated the proportion of guidelines mentioning or referencing COS and the proportion of COS domains specifically, or generally, matching to outcomes specified in each guideline populations, interventions, comparators and outcome (PICO) statement. RESULTS: We found 38 guidelines that contained 170 PICO statements matching the scope of the ten COS and of sufficient quality to allow data extraction. None of the guidelines reviewed explicitly mentioned or referenced the relevant COS. The median (range) of the proportion of core outcomes covered either specifically or generally by the guideline PICO was 30% (0%-100%). CONCLUSION: There is no evidence that COS are being used routinely to inform the guideline development process, and concordance between outcomes in published guidelines and those in COS is limited. Further work is warranted to explore barriers and facilitators in the use of COS when developing clinical guidelines.
Subject(s)
Outcome Assessment, Health Care , Practice Guidelines as Topic , Humans , Practice Guidelines as Topic/standards , Outcome Assessment, Health Care/standards , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , ConsensusABSTRACT
OBJECTIVE: We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD). DESIGN: Systematic review and network meta-analysis of randomised clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023. STUDY SELECTION: Interventional RCTs that enrolled patients presenting with chronic pain associated with TMD. DATA EXTRACTION AND SYNTHESIS: Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We captured all reported patient-important outcomes, including pain relief, physical functioning, emotional functioning, role functioning, social functioning, sleep quality, and adverse events. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence and categorise interventions from most to least beneficial. RESULTS: 233 trials proved eligible for review, of which 153-enrolling 8713 participants and exploring 59 interventions or combinations of interventions-were included in network meta-analyses. All subsequent effects refer to comparisons with placebo or sham procedures. Effects on pain for eight interventions were supported by high to moderate certainty evidence. The three therapies probably most effective for pain relief were cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy (risk difference (RD) for achieving the minimally important difference (MID) in pain relief of 1 cm on a 10 cm visual analogue scale: 36% (95% CI 33 to 39)), therapist-assisted jaw mobilisation (RD 36% (95% CI 31 to 40)), and manual trigger point therapy (RD 32% (29 to 34)). Five interventions were less effective, yet more effective than placebo, showing RDs ranging between 23% and 30%: CBT, supervised postural exercise, supervised jaw exercise and stretching, supervised jaw exercise and stretching with manual trigger point therapy, and usual care (such as home exercises, self stretching, reassurance).Moderate certainty evidence showed four interventions probably improved physical functioning: supervised jaw exercise and stretching (RD for achieving the MID of 5 points on the short form-36 physical component summary score: 43% (95% CI 33 to 51)), manipulation (RD 43% (25 to 56)), acupuncture (RD 42% (33 to 50)), and supervised jaw exercise and mobilisation (RD 36% (19 to 51)). The evidence for pain relief or physical functioning among other interventions, and all evidence for adverse events, was low or very low certainty. CONCLUSION: When restricted to moderate or high certainty evidence, interventions that promote coping and encourage movement and activity were found to be most effective for reducing chronic TMD pain. REGISTRATION: PROSPERO (CRD42021258567).
Subject(s)
Chronic Pain , Cognitive Behavioral Therapy , Humans , Chronic Pain/etiology , Chronic Pain/therapy , Network Meta-Analysis , Exercise Therapy/methods , Physical Therapy Modalities , Randomized Controlled Trials as TopicABSTRACT
The aim of this special article is to summarize and discuss, from an anesthesia perspective, the network meta-analysis on drugs used for the prevention of postoperative nausea and vomiting after general anesthesia, in agreement with the Cochrane Colombia collaboration and within the framework of the Cochrane Corners strategy. Through the combination of indirect comparisons and based on the evidence, the use of aprepitant, ramosetron, granisetron, dexamethasone and ondansetron is recommended with a high degree of certainty for the reduction of postoperative nausea and vomiting.
Este artículo especial tiene el objetivo de resumir y discutir desde la perspectiva de la anestesiología, el metaanálisis en red sobre fármacos para prevenir náuseas y vómito posoperatorio luego de anestesia general, en acuerdo con la colaboración Cochrane Colombia y en el marco de la estrategia Cochrane Corners. Mediante la combinación de la evidencia y el uso de comparaciones indirectas, se ha recomendado con alto grado de certeza el uso de aprepitant, ramosetrón, granisetrón, dexametasona y ondansetrón para la reducción de náuseas y vómito posoperatorio.
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BACKGROUND AND OBJECTIVE: Clinical practice guidelines (CPGs) are evaluated for quality with the Appraisal of Guidelines for Research and Evaluation (AGREE) tool, and this is increasingly done for different countries and regional groupings. This scoping review aimed to describe, map, and compare these geographical synthesis studies, that assessed CPG quality using the AGREE tool. This allowed a global interpretation of the current landscape of these country-wide or regional synthesis studies, and a closer look at its methodology and results. STUDY DESIGN AND METHODS: A scoping review was conducted searching databases Medline, Embase, Epistemonikos, and grey literature on 5 October 2021 for synthesis studies using the later versions of AGREE (AGREE II, AGREE-REX and AGREE GRS) to evaluate country-wide or regional CPG quality. Country-wide or regional synthesis studies were the units of analysis, and simple descriptive statistics was used to conduct the analysis. AGREE scores were analysed across subgroups into one of the seven Sustainable Development Goal regions, to allow for meaningful interpretation. RESULTS: Fifty-seven studies fulfilled our eligibility criteria, which had included a total of 2918 CPGs. Regions of the Global North, and Eastern and South-Eastern Asia were most represented. Studies were consistent in reporting and presenting their AGREE domain and overall results, but only 18% (n = 10) reported development methods, and 19% (n = 11) reported use of Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Overall scores for domains Rigor of development and Editorial independence were low, notably in middle-income countries. Editorial Independence scores, especially, were low across all regions with a maximum domain score of 46%. There were no studies from low-income countries. CONCLUSION: There is an increasing tendency to appraise country-wide and regionally grouped CPGs, using quality appraisal tools. The AGREE tool, evaluated in this scoping review, was used well and consistently across studies. Findings of low report rates of development of CPGs and of use of GRADE is concerning, as is low domain scores globally for Editorial Independence. Transparent reporting of funding and competing interests, as well as highlighting evidence-to-decision processes, should assist in further improving CPG quality as clinicians are in dire need of high-quality guidelines.
Subject(s)
Databases, Factual , Practice Guidelines as Topic , Practice Guidelines as Topic/standardsABSTRACT
Importance: Modulation of intestinal microbiome by administering probiotics, prebiotics, or both may prevent morbidity and mortality in premature infants. Objective: To assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials. Data Sources: MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023. Study Selection: Eligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants. Data Extraction and Synthesis: A frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach. Main Outcomes and Measures: All-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization. Results: A total of 106 trials involving 25â¯840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, -3.7%; 95% CI, -4.1% to -2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, -5.1%; 95% CI, -5.6% to -3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, -10.7%; 95% CI, -13.7% to -3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, -10.0%; 95% CI, -13.9% to -5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, -14.1%; 95% CI, -18.3% to -8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, -10.0%; 95% CI, -12.6% to -7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, -1.94 days; 95% CI, -2.96 to -0.92) and multistrain probiotics (MD, -2.03 days; 95% CI, -3.04 to -1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, -3.31 days; 95% CI, -5.05 to -1.58; and MD, -2.20 days; 95% CI, -4.08 to -0.31, respectively). Conclusions and Relevance: In this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.
Subject(s)
Enterocolitis, Necrotizing , Probiotics , Sepsis , Infant , Infant, Newborn , Humans , Infant, Premature , Lactoferrin/therapeutic use , Prebiotics , Enterocolitis, Necrotizing/prevention & control , Network Meta-Analysis , Probiotics/therapeutic use , Sepsis/prevention & control , Morbidity , OligosaccharidesABSTRACT
BACKGROUND AND OBJECTIVES: To determine whether the use of Evidence to Decision (EtD) frameworks is associated to higher quality of both guidelines and individual recommendations. METHODS: We identified guidelines recently published by international organizations that have methodological guidance documents for their development. Pairs of researchers independently extracted information on the use of these frameworks, appraised the quality of the guidelines using the Appraisal of Guidelines, Research and Evaluation II Instrument (AGREE-II), and assessed the clinical credibility and implementability of the recommendations with the Appraisal of Guidelines for REsearch & Evaluation Recommendations Excellence (AGREE-REX) tool. We conducted both descriptive and inferential analyses. RESULTS: We included 66 guidelines from 17 different countries, published in the last 5 years. Thirty guidelines (45%) used an EtD framework to formulate their recommendations. Compared to those that did not use a framework, those using an EtD framework scored higher in all domains of both AGREE-II and AGREE-REX (P < 0.05). Quality scores did not differ between the use of the The Grading of Recommendations Assessment, Development and Evaluation-EtD framework (17 guidelines) or another EtD framework (13 guidelines) (P > 0.05). CONCLUSION: The use of EtD frameworks is associated with guidelines of better quality, and more credible and transparent recommendations. Endorsement of EtD frameworks by guideline developing organizations will likely increase the quality of their guidelines.
Subject(s)
Evidence-Based Medicine , Research Personnel , HumansABSTRACT
OBJECTIVES: This article describes considerations for addressing intransitivity when assessing the certainty of the evidence from network meta-analysis (NMA) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Intransitivity is induced by effect modification, that is, when the magnitude of the effect between an intervention and outcome differs depending on the level of another factor. STUDY DESIGN AND SETTING: To develop this GRADE concept paper, the lead authors conducted iterative discussions, computer simulations, and presentations to the GRADE project group and at GRADE working group meetings. The GRADE Working Group formally approved the article in July 2022. RESULTS: NMA authors can have a higher or a lower threshold to rate down the certainty of the evidence due to intransitivity, which depends on the extent of their concerns regarding the trustworthiness of indirect comparisons, and their view of the relative problems with rating down excessively or insufficiently. NMA authors should consider three main factors when addressing intransitivity: the credibility of effect modification, the strength of the effect modification, and the distribution of effect modifiers across the direct comparisons. To avoid double counting limitations of the evidence, authors should consider the relationship between intransitivity and other GRADE domains. CONCLUSION: NMA authors face theoretic and pragmatic challenges and in most situations need to assess intransitivity without the availability of empirical data. Thus, explicitness regarding perspective is crucial.
Subject(s)
GRADE Approach , Humans , Network Meta-AnalysisABSTRACT
BACKGROUND: Evidence has shown that private industry-sponsored randomized controlled trials (RCTs) and meta-analyses are more likely to report intervention-favourable results compared with other sources of funding. However, this has not been assessed in network meta-analyses (NMAs). OBJECTIVES: To (a) explore the recommendation rate of industry-sponsored NMAs on their company's intervention, and (b) assess reporting in NMAs of pharmacologic interventions according to their funding type. METHODS: Design: Scoping review of published NMAs with RCTs. INFORMATION SOURCES: We used a pre-existing NMA database including 1,144 articles from MEDLINE, EMBASE and Cochrane Database of Systematic Reviews, published between January 2013 and July 2018. STUDY SELECTION: NMAs with transparent funding information and comparing pharmacologic interventions with/without placebo. SYNTHESIS: We captured whether NMAs recommended their own or another company's intervention, classified NMAs according to their primary outcome findings (i.e., statistical significance and direction of effect), and according to the overall reported conclusion. We assessed reporting using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension to NMA (PRISMA-NMA) 32-item checklist. We matched and compared industry with non-industry NMAs having the same research question, disease, primary outcome, and pharmacologic intervention against placebo/control. RESULTS: We retrieved 658 NMAs, which reported a median of 23 items in the PRISMA-NMA checklist (interquartile range [IQR]: 21-26). NMAs were categorized as 314 publicly-sponsored (PRISMA-NMA median 24.5, IQR 22-27), 208 non-sponsored (PRISMA-NMA median 23, IQR 20-25), and 136 industry/mixed-sponsored NMAs (PRISMA-NMA median 21, IQR 19-24). Most industry-sponsored NMAs recommended their own manufactured drug (92%), suggested a statistically significant positive treatment-effect for their drug (82%), and reported an overall positive conclusion (92%). Our matched NMAs (25 industry vs 25 non-industry) indicated that industry-sponsored NMAs had favourable conclusions more often (100% vs 80%) and were associated with larger (but not statistically significantly different) efficacy effect sizes (in 61% of NMAs) compared with non-industry-sponsored NMAs. CONCLUSIONS: Differences in completeness of reporting and author characteristics were apparent among NMAs with different types of funding. Publicly-sponsored NMAs had the best reporting and published their findings in higher impact-factor journals. Knowledge users should be mindful of this potential funding bias in NMAs.
Subject(s)
Checklist , Publications , Humans , Network Meta-Analysis , Bias , MEDLINEABSTRACT
BACKGROUND: Although acute diarrhoea is a self-limiting disease, dehydration may occur in some children. Dehydration is the consequence of an increased loss of water and electrolytes (sodium, chloride, potassium, and bicarbonate) in liquid stools. When these losses are high and not replaced adequately, severe dehydration appears. Severe dehydration is corrected with intravenous solutions. The most frequently used solution for this purpose is 0.9% saline. Balanced solutions (e.g. Ringer's lactate) are alternatives to 0.9% saline and have been associated with fewer days of hospitalization and better biochemical outcomes. Available guidelines provide conflicting recommendations. It is unclear whether 0.9% saline or balanced intravenous fluids are most effective for rehydrating children with severe dehydration due to diarrhoea. OBJECTIVES: To evaluate the benefits and harms of balanced solutions for the rapid rehydration of children with severe dehydration due to acute diarrhoea, in terms of time in hospital and mortality compared to 0.9% saline. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 4 May 2022. SELECTION CRITERIA: We included randomized controlled trials in children with severe dehydration due to acute diarrhoea comparing balanced solutions, such as Ringer's lactate or Plasma-Lyte with 0.9% saline solution, for rapid rehydration. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. time in hospital and 2. MORTALITY: Our secondary outcomes were 3. need for additional fluids, 4. total amount of fluids received, 5. time to resolution of metabolic acidosis, 6. change in and the final values of biochemical measures (pH, bicarbonate, sodium, chloride, potassium, and creatinine), 7. incidence of acute kidney injury, and 8. ADVERSE EVENTS: We used GRADE to assess the certainty of the evidence. MAIN RESULTS: Characteristics of the included studies We included five studies with 465 children. Data for meta-analysis were available from 441 children. Four studies were conducted in low- and middle-income countries and one study in two high-income countries. Four studies evaluated Ringer's lactate, and one study evaluated Plasma-Lyte. Two studies reported the time in hospital, and only one study reported mortality as an outcome. Four studies reported final pH and five studies reported bicarbonate levels. Adverse events reported were hyponatremia and hypokalaemia in two studies each. Risk of bias All studies had at least one domain at high or unclear risk of bias. The risk of bias assessment informed the GRADE assessments. Primary outcomes Compared to 0.9% saline, the balanced solutions likely result in a slight reduction of the time in hospital (mean difference (MD) -0.35 days, 95% confidence interval (CI) -0.60 to -0.10; 2 studies; moderate-certainty evidence). However, the evidence is very uncertain about the effect of the balanced solutions on mortality during hospitalization in severely dehydrated children (risk ratio (RR) 0.33, 95% CI 0.02 to 7.39; 1 study, 22 children; very low-certainty evidence). Secondary outcomes Balanced solutions probably produce a higher increase in blood pH (MD 0.06, 95% CI 0.03 to 0.09; 4 studies, 366 children; low-certainty evidence) and bicarbonate levels (MD 2.44 mEq/L, 95% CI 0.92 to 3.97; 443 children, four studies; low-certainty evidence). Furthermore, balanced solutions likely reduces the risk of hypokalaemia after the intravenous correction (RR 0.54, 95% CI 0.31 to 0.96; 2 studies, 147 children; moderate-certainty evidence). Nonetheless, the evidence suggests that balanced solutions may result in no difference in the need for additional intravenous fluids after the initial correction; in the amount of fluids administered; or in the mean change of sodium, chloride, potassium, and creatinine levels. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of balanced solutions on mortality during hospitalization in severely dehydrated children. However, balanced solutions likely result in a slight reduction of the time in the hospital compared to 0.9% saline. Also, balanced solutions likely reduce the risk of hypokalaemia after intravenous correction. Furthermore, the evidence suggests that balanced solutions compared to 0.9% saline probably produce no changes in the need for additional intravenous fluids or in other biochemical measures such as sodium, chloride, potassium, and creatinine levels. Last, there may be no difference between balanced solutions and 0.9% saline in the incidence of hyponatraemia.
Subject(s)
Dehydration , Hypokalemia , Child , Humans , Bicarbonates/therapeutic use , Creatinine , Dehydration/etiology , Dehydration/therapy , Diarrhea/therapy , Potassium , Potassium Chloride/therapeutic use , Ringer's Lactate , Saline Solution , SodiumABSTRACT
The COVID-19 pandemic has impacted parents' and children's well-being. This study aimed to evaluate the impact of the COVID-19 pandemic and its preventive measures on children's well-being and their parents' anxiety level. Parents/caregivers were invited to respond to a self-administered survey. The primary outcome was to assess the rate and severity of parental anxiety during the pandemic/lockdown. Four hundred and thirty parents completed the survey. Ninety-two (21%) and 10 (2%) parents reported that their children gained or lost weight during the pandemic, respectively. Eighty-one (19%) parents reported a regression in their children's developmental milestones, particularly in toileting, speech, and social interaction. The GAD-7 mean scores increased by 2.9 points (95% CI [2.5, 3.25]; P < .001) in comparison with prepandemic scores. Adjusted multivariable analysis showed that having children with psychological conditions and a maternal education level less than a university degree were significantly associated with higher parental anxiety.
Subject(s)
COVID-19 , SARS-CoV-2 , Child , Humans , Pandemics , Ontario/epidemiology , Caregivers/psychology , Communicable Disease Control , Parents/psychologyABSTRACT
OBJECTIVES: This study aims to identify existing reporting standards for child health research, assess the robustness of the standards development process, and evaluate the dissemination of these standards. STUDY DESIGN AND SETTING: We searched MEDLINE, the EQUATOR Network Library, and Google to identify reporting standards for child health research studies. We assessed the adherence of the Guidance for Developers of Health Research Reporting Guidelines (GDHRG) by the identified reporting standards. We also assessed the use of the identified reporting standards by primary research studies, and the endorsement of the included reporting standards by journals. RESULTS: We identified six reporting standards for child health research, including two under development. Among the four available standards their median adherence to the 18 main steps of the GDHRG was 58.35% (range: 27.8%-83.3%). None of these four reporting standards had been endorsed by pediatric journals indexed by the Science Citation Index. Only 26 primary research studies declared that they followed one of the reporting standards. CONCLUSION: There is a quantitative and qualitative paucity of well-developed reporting standards for child health research. The available standards are also poorly implemented. This situation demands an urgent need to develop robust standards and ensure their implementation.